A phase Ib/II trial evaluating the combination of TG4001 and avelumab in patients with HPV-16 positive recurrent or metastatic malignancies

Transgene17 sites in 2 countries142 target enrollmentJuly 16, 2024

DrugsBavencio 20 mg/mL concentrate for solution for infusion TG4001 Recombinant human monoclonal IgG1 antibody against programmed death ligand-1 MSB 0010718C MSB0010718C

Overview

Phase: Phase 1/2
Intervention: Not specified
Conditions: Not specified
Sponsor: Transgene
Enrollment: 142
Locations: 17
Primary Endpoint: Phase II part 1: overall response rate according to RECIST 1.1
Status: Active, not recruiting
Last Updated: 11 months ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

Phase Ib objective: To evaluate the safety and tolerability of the combination of TG4001 plus avelumab in patients with recurrent or metastatic HPV-16 positive advanced malignancies. Phase II part 1 objective: To evaluate the efficacy of TG4001 combined to avelumab in terms of Overall Response Rate (ORR) by using RECIST 1.1 in patients with recurrent or metastatic (R/M) HPV-16 positive advanced malignancies including oropharyngeal squamous cell carcinoma of head and neck. Phase II part 2 objective: To compare the Progression-Free Survival (PFS) of TG4001 in combination with avelumab vs avelumab alone in patients with recurrent or metastatic (R/M) HPV-16 positive advanced malignancies and without liver metastases at baseline.

Registry

euclinicaltrials.eu

Start Date

July 16, 2024

End Date

TBD

Last Updated

11 months ago

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

Transgene

Responsible Party

Principal Investigator

Transgene Medical Affairs

Scientific

Transgene

Eligibility Criteria

Inclusion Criteria

•Female or male patients, aged at least 18 years (no upper limit of age)
•Negative blood pregnancy test at screening for women of childbearing potential
•Highly effective contraception for both male and female patients if the risk of conception exists during the study period and for 3 months after the last study treatment administration
•ECOG PS 0 or 1
•Life expectancy of at least 3 months
•Phase Ib and Phase II part 1: Patients with histologically or cytologically documented metastatic or refractory/recurrent HPV-16 + cancer (cervical, vulvar, vaginal, penile, anal cancers and oropharyngeal squamous cell carcinoma of head and neck); Phase II part 2: Patients with HPV-16+ cancers including cervical, vulvar, vaginal, penile, and anal cancer
•Disease MUST not be amenable to curative surgery resection or curative radiotherapy with documented disease progression
•Prior therapy: Phase Ib and Phase II part 1: Patients MAY have received up to 2 prior lines of systemic chemotherapy for the management of metastatic or recurrent disease; for SCCHN, patients MUST have previously been exposed to platinum-based therapy, either as part of definitive chemoradiation OR as first line systemic treatment for metastatic disease which may include cetuximab. Patients with recurrence/progression within 6 months of prior multimodal therapy using platinum-based therapy are eligible. Patients with cervical cancer may have undergone surgery and/or received definitive radiation or chemo-radiation therapy for localized disease. Phase II part 2: - No more than one prior systemic treatment for recurrent /metastatic disease - Prior treatment for recurrent or metastatic disease is not required for: o Patients with recurrence/progression within 6 months after completion of prior multimodal therapy for localized or locally advanced disease o Patients who are unsuitable for platinum-based therapy o Patients who refuse chemotherapy or other standard therapies for the treatment of metastatic or recurrent disease
•For patients with hepatic metastases - no more than 3 hepatic lesions in total (target and non-target lesions) - maximum size of hepatic target disease ≤ 30 mm according to RECIST 1.1
•At least one measurable lesion by CT scan according to RECIST 1.

Exclusion Criteria

•Prior exposure to cancer immunotherapy including cancer vaccines, any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
•Patients with history of interstitial lung disease
•Patients with active, known, or suspected auto-immune disease or immunodeficiency, except type I diabetes mellitus, hypothyroidism only requiring hormone replacement or skin disorders (such as vitiligo, psoriasis) not requiring systemic treatment
•Significant chronic or acute infections including SARS-CoV-2 (COVID19) PCR positive testing
•Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction (< 6 months prior to enrollment), unstable angina pectoris, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication/active intervention
•History of uncontrolled intercurrent illness including but not limited to: - Hypertension uncontrolled by standard therapies (not stabilized to 150/90 mmHg or lower) - Uncontrolled diabetes (e.g., hemoglobin A1c ≥ 8%)
•Patients under chronic treatment with systemic corticosteroids or other immunosuppressive drugs for a period of at least 4 weeks and whose treatment was not stopped 2 weeks prior to the first study treatment, with the exception of patients with adrenal insufficiency who may continue corticosteroids at physiological replacement dose, equivalent to ≤ 10 mg prednisone daily. Steroids with no or minimal systemic effect (topical, inhalation) are allowed
•Patients with CNS metastases except those with brain metastases treated locally and clinically stable during 4 weeks prior to start of study treatment, and those without ongoing neurological symptoms that are related to the brain localization of the disease
•Other active malignancy requiring concurrent systemic intervention
•Patients with previous malignancies other than the target malignancy to be investigated in this trial (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period

Outcomes

Primary Outcomes

Phase II part 1: overall response rate according to RECIST 1.1

Phase II part 2: progression-free survival according to RECIST 1.1

Phase Ib: safety and tolerability

Secondary Outcomes

Phase Ib: Overall response rate by using RECIST 1.1 and overall safety profile
Phase Ib and phase II part 2: Overall response rate by using RECIST 1.1
Phase Ib and phase II part 1: Progression Free Survival (PFS)
Overall Survival (OS)
Duration of Response (DoR)
Overall safety profile
Percentage of patients with liver metastases at baseline who have disease progression at D43 (phase II part 2)